Evaluation the role of TSHR gene polymorphisms and DNA methylation in the pathogenesis of autoimmune thyroid disease among the Iraqi via statistical methods

This study was aimed to determine the association of polymorphism of TSHR gene with incidence of Graves' disease (GD) in Iraqi patients. This study was carried out in the Institute of Genetic Engineering and Biotechnology for Postgraduate Studies - University of Baghdad and samples were collected from Endocrinology and Diabetes Centre /Al-Kindy Hospital. the three TSHR gene SNPs presented seven possible haplotypes with ACC as the most common in both groups (patients and controls). In particular, the GCC haplotype showed statistically significant (p<0.01) increase in Autoimmune Thyroid Disease patients and a decrease in apparently healthy controls. The results showed that the frequency of GCC / GCC haplotype combination was significantly (p<0.05) higher in Autoimmune Thyroid Disease patients than in apparently healthy controls. This haplotype combination means that homozygous mutant (GG) of rs179247 SNP of TSHR gene is at risk with Graves' disease in Iraqi patients. Hormonal analysis for T3, T4 , TSH and Anti TSHR Ab was performed using Automated Immune Assay (AIA).These results indicate that serum T3 , T4 and Anti TSHR Ab concentrations were unaffected by the studied SNPs of TSHR gene within carriers of genotypes of rs179247 , rs2268458 and rs12101255 SNPs in TSHR gene. At the same time serum T3 and T4 levels were significantly higher in GD patients than in controls. The result of serum TSH concentration affected only in healthy controls and its shown increasing in serum TSH levels in GG carriers of SNP rs179247 in TSHR when compared with AA and AG genotypes. In GD patients, there was a significant increase in serum TSH levels in TT carriers of SNP rs12101255 in TSHR compared with CC and CT genotypes. Serum TSH levels were significantly lower in Autoimmune Thyroid Disease patients than in apparently healthy subjects.